Suppressor of cytokine signaling (SOCS)-1 is expressed in human prostate cancer and exerts growth-inhibitory function through down-regulation of cyclins and cyclin-dependent kinases

Am J Pathol. 2009 May;174(5):1921-30. doi: 10.2353/ajpath.2009.080751. Epub 2009 Mar 26.


Suppressor of cytokine signaling (SOCS) proteins play a pivotal role in the development and progression of various cancers. We have previously shown that SOCS-3 is expressed in prostate cancer, and its expression is inversely correlated with activation of signal transducer and activator of transcription factor 3. We hypothesized that SOCS-1, if expressed in prostate cancer cells, has a growth-regulatory role in this malignancy. The presence of both SOCS-1 mRNA and protein was detected in all tested cell lines. To assess SOCS-1 expression levels in vivo, we analyzed tissue microarrays and found a high percentage of positive cells in both prostate intraepithelial neoplasias and cancers. SOCS-1 expression levels decreased in samples taken from patients undergoing hormonal therapy but increased in specimens from patients who failed therapy. In LNCaP-interleukin-6- prostate cancer cells, SOCS-1 was up-regulated by interleukin-6 and in PC3-AR cells by androgens; such up-regulation was also found to significantly impair cell proliferation. To corroborate these findings, we used a specific small interfering RNA against SOCS-1 and blocked expression of the protein. Down-regulation of SOCS-1 expression caused a potent growth stimulation of PC3, DU-145, and LNCaP-interleukin-6- cells that was associated with the increased expression levels of cyclins D1 and E as well as cyclin-dependent kinases 2 and 4. In summary, we show that SOCS-1 is expressed in prostate cancer both in vitro and in vivo and acts as a negative growth regulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androgens / pharmacology
  • Blotting, Western
  • Cyclin D1 / metabolism*
  • Cyclin E / metabolism*
  • Cyclin-Dependent Kinases / metabolism*
  • Down-Regulation
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-6 / pharmacology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Intraepithelial Neoplasia / genetics
  • Prostatic Intraepithelial Neoplasia / metabolism
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / antagonists & inhibitors
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Tissue Array Analysis
  • Tumor Cells, Cultured


  • Androgens
  • CCND1 protein, human
  • Cyclin E
  • Interleukin-6
  • RNA, Messenger
  • RNA, Small Interfering
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinases